Survival Prediction of Clear Cell Renal Cell Carcinoma Based on Gene Expression Similarity to the Proximal Tubule of the Nephron

Büttner, Florian; Winter, Stefan; Rausch, Steffen; Reustle, Anna; Kruck, Stephan; Junker, Kerstin; Stenzl, Arnulf; Agaimy, Abbas; Hartmann, Arndt; Bedke, Jens; Schwab, Matthias; Schaeffeler, Elke

doi:10.1016/j.eururo.2015.05.045

Cited by 57 publications

(89 citation statements)

References 12 publications

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“…Therefore, the present study aimed to analyze the prognostic value of SOX genes in patients with RCC using public database and validate these findings in a patient cohort. (17). Finally, 505 patients confirmed with primary clear cell RCC with detailed SOX expression data were included in the current study.…”

Section: Introductionmentioning

confidence: 99%

SOX2 and SOX12 are predictive of prognosis in patients with clear cell renal cell carcinoma

Wang

Wan

et al. 2018

Oncol Lett

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Abstract. Sex-determining region Y-box protein (SOX) genes serve an important role in cancer growth and metastasis. The present study aimed to determine the predictive ability of SOX and associated genes identified through molecular network in clear cell renal cell carcinoma (RCC). A total of 505 patients with clear cell RCC from The Cancer Genome Atlas (TCGA) cohorts were collected in this study. The expression profile of SOX and associated genes were obtained from the TCGA RNAseq database. Clinicopathological characteristics, including age, gender, tumor grade, stage, laterality disease-free-survival and overall survival (OS) were collected. Cox's proportional hazards regression model, as well as Kaplan-Meier curves were used to assess the relative factors. Selected genes of SOXs that demonstrated significant associations with OS were further validated in 192 patients from the validation cohort. In the univariate Cox regression model, SOX1, SOX2, SOX6, SOX11, SOX12, SOX13, SOX15, SOX17 and SOX30 expression were predictive in the prognosis of clear cell RCC. Following adjustment for clinical factors, SOX2 [hazard ratio (HR), 1.130; 95% confidence interval (CI), 1.002-1.275), SOX12 (HR, 1.379; 95% CI, 1.060-1.793) and SOX15 (HR, 1.245; 95% CI, 1.063-1.459) remained statistically significant. Furthermore, POU class 5 homeobox 1 (POU5F1), POU2F1 and nuclear receptor subfamily 5 group A member 1 in the gene cluster network analysis associated with SOX2 did not reduce the statistical significance when added to the multivariate analysis. The findings were extended to the Fudan University Shanghai Cancer Center cohort. The results revealed that high SOX2 and SOX12 expression were associated with poor prognosis for OS (log-rank test, all P<0.05). SOX2 and SOX12 were identified as independent prognostic factors of OS in clear cell RCC.

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Section: Introductionmentioning

confidence: 99%

SOX2 and SOX12 are predictive of prognosis in patients with clear cell renal cell carcinoma

Wang

Wan

et al. 2018

Oncol Lett

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“…Research is moving a step further by exploring the novel dimension of genotype-phenotype associations in human cancers through the integration of advanced molecular platforms and computational analysis of whole-slide imaging [8]. This approach can substantively improve our understanding of the biology of tumor by correlating molecular changes with morphologic characteristics including cell-stroma relationships and tumor microenvironment.As much as the paper by Bü ttner et al [2] highlights the great promise of molecular pathology, it also emphasizes that the journey from bench to bedside is still a work in progress. As noted by the authors, validation with large E U R O P E A N U R O L O G Y X X X ( 2 0 1 5 ) X X X -X X X a v a i l a b l e a t w w w .…”

mentioning

confidence: 95%

“…As much as the paper by Bü ttner et al [2] highlights the great promise of molecular pathology, it also emphasizes that the journey from bench to bedside is still a work in progress. As noted by the authors, validation with large E U R O P E A N U R O L O G Y X X X ( 2 0 1 5 ) X X X -X X X a v a i l a b l e a t w w w .…”

mentioning

confidence: 95%

“…The introduction of molecular profiling approaches that enable simultaneous analysis of thousands of molecules marked a new milestone in patient management in kidney and other cancers [1]. This development will lead to substantial improvement of outcome by customizing the management plan for each patient based on the molecular biology of the tumor, as manifested by the molecular expression profile.In this month's issue of European Urology, Bü ttner et al identified a molecular signature, named the S3-score, that enables prognostic risk stratification of clear cell renal cell carcinoma (ccRCC) [2]. In this elegant study, the authors hypothesized that the degree of divergence of ccRCC from its cell of origin in the nephron correlates with cancerspecific survival.…”

mentioning

confidence: 98%

“…In this month's issue of European Urology, Bü ttner et al identified a molecular signature, named the S3-score, that enables prognostic risk stratification of clear cell renal cell carcinoma (ccRCC) [2]. In this elegant study, the authors hypothesized that the degree of divergence of ccRCC from its cell of origin in the nephron correlates with cancerspecific survival.…”

mentioning

confidence: 98%

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Personalized Medicine in Kidney Cancer: Learning How to Walk Before We Run

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Renal cancer subtypes: Should we be lumping or splitting for therapeutic decision making?

Rathmell

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The treatment of advanced renal cell carcinoma has posed a challenge for decades, in part because of common themes related to intrinsic resistance to cytotoxic chemotherapy, and the obscure biology of these cancer types. Forward movement in the treatment of the renal cell carcinomas can thus be approached in two ways: splitting the tumor types along histologic and molecular features, in the hopes of coupling highly precision-focused therapy on a subset of disease with most potential for benefit, or lumping the various biologies and histologies together, in order to carry the rarer renal cell carcinoma types with more common disease. The former strategy satisfies our desire for customized precision in treatment delivery, while the latter strategy allows us to offer a wider therapeutic menu in a set of diseases we are continuing to learn about on a physiologic and molecular level.

show abstract

Survival Prediction of Clear Cell Renal Cell Carcinoma Based on Gene Expression Similarity to the Proximal Tubule of the Nephron

Cited by 57 publications

References 12 publications

SOX2 and SOX12 are predictive of prognosis in patients with clear cell renal cell carcinoma

SOX2 and SOX12 are predictive of prognosis in patients with clear cell renal cell carcinoma

Personalized Medicine in Kidney Cancer: Learning How to Walk Before We Run

Renal cancer subtypes: Should we be lumping or splitting for therapeutic decision making?

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